Dataset Information

LncRNA NNT-AS1 promotes lung squamous cell carcinoma progression by regulating the miR-22/FOXM1 axis.

ABSTRACT:

Background

Recent studies have revealed that dysregulated expression of long non-coding RNA nicotinamide nucleotide transhydrogenase antisense RNA 1 (lncRNA NNT-AS1) is associated with cell tumorigenicity in non-small cell lung cancer. However, the exact molecular mechanisms of NNT-AS1 in lung squamous cell carcinoma (LUSC) remain largely unknown.

Methods

The expression of NNT-AS1, microRNA (miR)-22 and Forkhead box protein M1 (FOXM1) was measured using quantitative real-time polymerase chain reaction or western blot, respectively. The interaction between miR-22 and NNT-AS1 or FOXM1 was confirmed using a dual-luciferase reporter assay and RNA immunoprecipitation assay. Cell migration and invasion abilities were measured by Transwell assay. Flow cytometry was used to detect apoptotic cells.

Results

NNT-AS1 and FOXM1 were up-regulated but miR-22 was down-regulated in LUSC tissues and cell lines. NNT-AS1 was a sponge of miR-22, and NNT-AS1 deletion suppressed the migration and invasion but induced apoptosis in LUSC cells. FOXM1 was a target of miR-22, and overexpression of miR-22 inhibited cell carcinogenesis in LUSC by targeting FOXM1. Additionally, NNT-AS1 could directly regulate FOXM1 expression by binding to miR-22 in LUSC cells.

Conclusion

LncRNA NNT-AS1 contributes to cell carcinogenesis in LUSC by regulating the miR-22/FOXM1 axis, providing a novel insight into the pathogenesis of LUSC and a new potential therapeutic target for LUSC treatment.

SUBMITTER: Ma J

PROVIDER: S-EPMC7257167 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

LncRNA NNT-AS1 promotes lung squamous cell carcinoma progression by regulating the miR-22/FOXM1 axis.

Ma Jing J Qi Guanbin G Li Lei L

Cellular & molecular biology letters 20200529

<h4>Background</h4>Recent studies have revealed that dysregulated expression of long non-coding RNA nicotinamide nucleotide transhydrogenase antisense RNA 1 (lncRNA NNT-AS1) is associated with cell tumorigenicity in non-small cell lung cancer. However, the exact molecular mechanisms of NNT-AS1 in lung squamous cell carcinoma (LUSC) remain largely unknown.<h4>Methods</h4>The expression of NNT-AS1, microRNA (miR)-22 and Forkhead box protein M1 (FOXM1) was measured using quantitative real-time poly ...[more]

PMID: 32514270

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Project description:Long non-coding RNA (lncRNA) is essential to the development and progression of malignant human cancer. Growing evidence suggests that the lncRNA forkhead box D3 antisense 1 (FOXD3-AS1) is a crucial regulatory effector for multiple cancer types and is closely associated with poor prognosis. However, in most cases, the molecular mechanism underlying the role of FOXD3-AS1 in cancer development has not yet been fully elucidated. The present study focused on non-small cell lung cancer (NSCLC) in order to gain insight into how FOXD3-AS1 drives cancer progression. First, FOXD3-AS1 expression in NSCLC tissue samples was detected using reverse transcription-quantitative (RT-qPCR). Moreover, cell proliferation and apoptosis were determined using Cell Counting Kit-8 assays and flow cytometry, respectively. A luciferase reporter assay was then performed to determine whether there was a direct binding association between FOXD3-AS1 and microRNA (miR)-135a-5p. Lastly, a tumor subcutaneous xenograft model was established to examine the role of FOXD3-AS1 in tumor growth. FOXD3-AS1 was significantly overexpressed in NSCLC tissue samples and cell lines compared with normal tissue samples and cells. FOXD3-AS1 silencing expression significantly inhibited A549 and H1229 cell proliferation while inducing apoptosis compared with sh-NC group. The luciferase reporter assay demonstrated the direct binding interaction between FOXD3-AS1 and miR-135a-5p. Moreover, FOXD3-AS1 silencing led to the upregulation of miR-135a-5p in A549 and H1229 cells compared with sh-NC group. It was also demonstrated that miR-135a-5p could bind to the 3' untranslated region of cyclin-dependent kinase 6 (CDK6) and negatively modulate its transcription. miR-135a-5p knockdown or CDK6 overexpression reversed the inhibition on cell proliferation and apoptosis following FOXD3-AS1 knockdown. Altogether, the present study suggests that FOXD3-AS1 sponges miR-135a-5p to promote cell proliferation and concomitantly inhibit apoptosis by regulating CDK6 expression in NSCLC cells.

Dataset Information

LncRNA NNT-AS1 promotes lung squamous cell carcinoma progression by regulating the miR-22/FOXM1 axis.

Background

Methods

Results

Conclusion

Publications

LncRNA NNT-AS1 promotes lung squamous cell carcinoma progression by regulating the miR-22/FOXM1 axis.

Similar Datasets

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